Plasma YKL-40 as a biomarker for bevacizumab efficacy in patients with newly diagnosed glioblastoma in the phase 3 randomized AVAglio trial
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Mogens K. Boisen1, Camilla B. Holst2, Nicola Consalvo3, Olivier L. Chinot4 and Julia S. Johansen1,2,5
1Department of Oncology, Herlev University Hospital, Herlev and Gentofte Hospital, Copenhagen, Denmark
2Department of Medicine, Herlev University Hospital, Herlev, and Gentofte Hospital, Copenhagen, Denmark
3Biostatistics, F. Hoffmann-La Roche Ltd, Basel, Switzerland
4Department of Neuro-Oncology, Aix-Marseille University, Marseille, France
5Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Mogens K. Boisen, email: [email protected]
Keywords: bevacizumab; YKL-40; newly-diagnosed; glioblastoma; AVAglio
Received: May 07, 2017 Accepted: November 14, 2017 Published: December 04, 2017
YKL-40 is a glycoprotein with pro-angiogenic functions. We hypothesized that patients with newly diagnosed glioblastoma and low baseline plasma YKL-40 levels derive greater benefit from first-line bevacizumab. Plasma samples were collected from 563 patients in the randomized, phase 3 AVAglio trial who received bevacizumab or placebo plus radiotherapy/temozolomide. Raw plasma YKL-40 concentrations were converted to age-corrected percentiles of normal healthy YKL-40 levels and divided into quartiles (Q). The impact of baseline plasma YKL-40 level on survival was investigated using Cox regression analyses. Patients with low baseline plasma YKL-40 (≤Q1) had an improved progression-free survival hazard ratio (HR) for bevacizumab versus placebo (0.37, 95% confidence interval [CI]: 0.25–0.55) compared with high plasma YKL-40 (> Q1) (0.71, 95% CI: 0.57–0.87). Overall survival HRs were comparable between the subgroups (≤ Q1: 0.69, 95% CI: 0.44–1.09; (> Q1: 0.88, 95% CI: 0.68–1.13). A trend for improved progression-free survival HR with low versus high YKL-40 was observed in proneural glioblastoma (0.41, 95% CI: 0.13–1.28 vs 0.80, 95% CI: 0.45–1.40, respectively), but not for proliferative/mesenchymal subtypes. Elevated plasma YKL-40 (> 90th percentile of normal) was an independent negative prognostic factor. In conclusion, the predictive value of baseline plasma YKL-40 level as a biomarker for bevacizumab efficacy in glioblastoma may be limited to patients with proneural tumors. Independent validation studies are required to confirm these results.
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